PATHOLOGY OF THE DIGESTIVE SYSTEM - The BASICS - Celia Marginean, MD DIGESTIVE SYSTEM 1. GASTRO-INTESTINAL (GI) TRACT: ESOPHAGUS STOMACH SMALL INTESTINE (DUODENUM, JEJUNUM, ILEUM) LARGE INTESTINE (COLON) RECTUM ANAL CANAL APPENDIX 2. LIVER 3. PANCREAS 4. GALLBALDER DIGESTIVE SYSTEM A). Ingestion B). Mechanical C). Chemical Ingestion D). Absorption E). Defecation F). Propulsion Alimentary canal is a hollow tube The wall has 4 layers: - Mucosa – epithelium, lamina propria, muscularis mucosae - Submucosa - Muscularis propria – two layers - Serosa (adventitia) ESOPHAGUS ESOPHAGUS 25 cm length Continues oropharynx to GEJ Swallowed food passes through pharynx into esophagus down to stomach Propulsion and peristalsis of esophagus ESOPHAGUS Squamous epithelium Submucosa with mucus secreting glands Muscularis propria (inner circular and outer longitudinal layers ) ESOPHAGUS - PATHOLOGY INFLAMMATION / INFECTIONS (Esophagitis) DISORDERS OF PERISTALTIS VASCULAR LESIONS TRAUMA NEOPLASIA ESOPHAGITIS Epithelial damage due to inflammation Most common cause is gastroesophageal reflux -GERD- (reflux of gastric contents into lower esophagus) Infectious causes are much less common - Candida, herpes virus, CMV, bacteria (immunocompromised) Chemical (erosive) esophagitis - acids, alkali Reflux esophagitis Most common; due to reflux of gastric contents into lower esophagus Physiology: chronic exposure to gastric juices (acid) impairs reparative capacity of esophageal mucosa Clinical : heartburn, regurgitation, pain (may be mistaken for myocardial infarction) Reflux esophagitis Incidence 3-4% in general population Usually in adults over age 40 Long term consequences are bleeding (almost never massive), stricture, Barrett’s esophagus (intestinal metaplasia) Gross: severe cases exhibit hyperemic mucosa with focal hemorrhage Reflux esophagitis normal - hyperplastic vascular papillae - basal hyperplasia - intraepithelial eosinophils - parakeratosis. Candida esophagitis Most common cause of infectious esophagitis Associated with antibiotic use in non-immunocompromised Usually due to Candida albicans Note: fungal invasion a requirement for diagnosis since Candida is normal flora in GI tract Often associated with CMV or HSV esophagitis Endoscopy: gray-white pseudomembrane or plaques in mid- to distal esophagus; mucosa is erythematous, edematous, ulcerated or friable Herpes esophagitis Usually an opportunistic infection in immunosuppressed patients May also have secondary bacterial or fungal infections Self-limited in healthy patients; may cause esophageal perforation or disseminate in immunocompromised patients Gross: shallow vesicles and ulcers; may coalesce into extensive areas of erosion Micro: ulcers contain necrotic debris and exudate with neutrophils; viral inclusions present in multinucleated squamous cells at margin of ulcer Barrett’s esophagus Distal squamous mucosa is replaced by metaplastic columnar epithelium (intestinal type) as a response to prolonged injury; columnar epithelium may be more resistant to acid, pepsin and bile Mean age at diagnosis is 60+; usually men Major risk factor for esophageal adenocarcinoma Symptoms: long history of heartburn and other reflux symptoms Treatment: anti-reflux therapy; endoscopy every 1-2 years to detect dysplasia or early adenocarcinoma Barrett’s esophagus Diagnosis: endoscopic : - areas of erythema (redness) - normal esophagus is white-pale histologic findings: - replacement of squamous epithelium with intestinal type columnar epithelium, with goblet cells (mucin containing) BARRETT’S ESOPHAGUS Alcian blue/PAS - stains goblet cells mucin in blue WHY IS BARRETT’S ESOPHAGUS IMPORTANT??? 1. Develops in 10% of adults with chronic reflux 2. Results in a 30-40 fold increase in risk of esophageal adenocarcinoma (5% lifetime risk) ; High risk of adenocarcinoma if > 2 cm of Barrett mucosa 3. Steps to development of adenocarcinoma: - low grade dysplasia - high grade dysplasia - carcinoma BARRETT’S ESOPHAGUS low grade dysplasia BARRETT’S ESOPHAGUS high grade dysplasia ESOPHAGUS - ADENOCARCINOMA - 30-40% of primary esophageal cancers; Age 40- 50, usually white men Symptoms: none or gastroesophageal reflux disease Arises at GEJ 5 year survival 15-25%, up to 80% with superficial disease and resection 85% arise in setting of Barrett’s esophagus; rarely arise from ectopic gastric mucosa in upper esophagus or from submucosal glands ESOPHAGUS - ADENOCARCINOMA - ESOPHAGUS - SQUAMOUS CELL CARCINOMA - Most common type of esophageal cancer Causes: alcohol, tobacco, urban environment Usually men age 50+ in low risk areas; more common in blacks (4:1) in US Symptoms: dysphagia, anorexia, weight loss (due to advanced stage at presentation) 90% in mid/lower esophagus Distant metastases to lungs, liver, bones, adrenal glands SQUAMOUS CELL CARCINOMA SQUAMOUS CELL CARCINOMA STOMACH v STOMACH The esophagus joins the stomach obliquely at the cardia (GEJ). The stomach is divided into the following parts: - Cardia - Fundus - Body - Antrum - Pylorus STOMACH NORMAL GROSS APPEARANCE Stomach Chemical digestion Mechanical digestion Propulsion (gastric emptying) Stomach- normal histology STOMACH – the cells parietal or oxyntic cells secrete hydrochloric acid and intrinsic factor, a substance essential for the absorption of Vitamin B12 in the small intestine ; peptic or chief cells secrete pepsinogen(inactive) which in contact with acid converts it to the active form pepsin ; mucous cells secrete a bicarbonate rich mucous which protects the stomach from the Hydrochloric acid of the gastric juice ; G cells (found only in the antral glands) secrete the hormone Gastrin. STOMACH - PATHOLOGY Inflammation of gastric mucosa - Gastritis Infections Peptic ulcer disease Polyps and polyposis syndromes Tumors: benign, malignant GASTRITIS ACUTE GASTRITIS CHRONIC GASTRITIS: NONATROPHIC G: - DIFFUSE ANTRAL CG, H.PYLORI RELATED ATROPHIC G: - AUTOIMMUNE ATROPHIC CG - MULTIFOCAL ATROPHIC CG REACTIVE GASTROPATHY (CHEMICAL G) : - NSAID - BILE REFLUX - VASCULAR GASTROPATHY Chronic gastritis Chronic mucosal inflammation leading to mucosal atrophy and intestinal metaplasia, usually without erosions The epithelial changes may become dysplastic and constitute a background for the development of carcinoma (low grade dysplasia-high grade dysplasia-carcinoma sequence) Most cases are non-autoimmune gastritis (non-atrophic) Associated with chronic Helicobacter pylori infection, toxins (alcohol, tobacco), reflux of bilious duodenal secretions (post-antrectomy or other), obstruction (bezoars, atony), radiation Incidence increases with age CHRONIC GASTRITIS – H.pylori related H pylori gastritis -diagnosis Non invasive: - blood antibody test - stool antigen test - carbon urea breath test (in which the patient drinks 14C- or 13C-labelled urea, which the bacterium metabolizes, producing labelled carbon dioxide that can be detected in the breath) - urine ELISA test ( 96% sensitivity , 79% specificity) Invasive: a biopsy during endoscopy- gold standard - HELICOBACTER PYLORI- Gram negative short spiraled bacilli arranged in groups within the mucus It was identified in 1982 by Barry Marshall and Robin Warren (they won Nobel prize) H.Pylori plays a critical role in : - Chronic gastritis - Peptic ulcer disease - Gastric carcinoma (risk 2% to 4%) - Gastric MALT lymphoma H pylori gastritis To colonize the stomach, H. pylori must survive the acidic pH of the lumen and use its flagella to burrow into the mucus to reach its niche Swims away from the acidic contents of the lumen towards the more neutral pH environment of the epithelial cell surface H. pylori produces large amounts of the enzyme urease, which breaks down urea (which is normally secreted into the stomach) to carbon dioxide and ammonia. The ammonia is converted to ammonium by accepting a proton (H+), which neutralizes gastric acid. The ammonia produced is toxic to the epithelial cells Peptic ulcer disease Colonization of the stomach by H. pylori results in chronic gastritis. Duodenal and stomach ulcers result when acid and pepsin in the stomach lumen overwhelm the protective mechanisms. The acidity within the stomach lumen affects the colonization pattern of H. pylori, and therefore ultimately determines whether a duodenal or gastric ulcer will form. Risk factors Pathophysiology Physiologic balance - between gastric acid secretion and gastroduodenal mucosal defense. Mucosal injury and peptic ulcer occur when the balance between the aggressive factors and the defensive mechanisms is disrupted. Aggressive factors: NSAIDs, H pylori infection, alcohol, bile salts, acid, and pepsin, can alter the mucosal defense by allowing back diffusion of hydrogen ions and subsequent epithelial cell injury. The defensive mechanisms: tight intercellular junctions, mucus, mucosal blood flow, cellular restitution, and epithelial renewal. Peptic ulcer disease Epigastric pain is the most common symptom of both gastric and duodenal ulcers. Burning sensation and occurs after meals—classically, shortly after meals with gastric ulcer and 2-3 hours afterward with duodenal ulcer. Upper GI endoscopy is the preferred diagnostic test Endoscopy - visualize the ulcer, biopsy, to determine presence and degree of active bleeding and presence of malignancy GASTRIC NEOPLASMS BENIGN: - POLYPS - HYPERPLASTIC - INFLAMMATORY - HAMARTOMATOUS - HETEROTOPIC - EPITHELIAL - NONEPITHELIAL MALIGNANT: - ADENOCARCINOMA - INTESTINAL TYPE - DIFFUSE TYPE - MESENCHYMAL TUMORS